Cross-reactivity of two SARS-CoV-2 serological assays in a malaria-endemic setting

34 Background: Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. 35 However, previous studies have indicated possible cross-reactivity of these assays, including in 36 malaria-endemic areas. 37 Methods: We tested 213 well-characterized pre-pandemic samples from Nigeria using two 38 SARS-CoV-2 serological assays: Abbott Architect IgG and Euroimmun NCP IgG assay, both 39 targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity 40 assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. 41 Results: Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on 42 the Euroimmun assay were positive. Anti-Plasmodium IgG levels were significantly higher 43 among false-positives for both Abbott and Euroimmun; no association was found with active P. 44 falciparum infection. An avidity assay using various concentratIons of urea wash in the 45 Euroimmun assay reduced loosely-bound IgG: of 37 positive/borderline pre-pandemic samples, 46 46%, 86%, 89%, and 97% became negative using 2M, 4M, 5M, and 8M urea washes, 47 respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 48 28 days of PCR confirmation; thereafter avidity increased for all urea concentrations except 8M. 49 on A ril 7, 2021 by gest ht://jcm .sm .rg/ D ow nladed fom